Download An overview of lung cancer

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November is Lung Cancer Awareness Month. With public smoking bans springing up over Europe and investment in campaigns to
discourage the habit in the UK, perhaps more of the future generation will see smoking as unattractive. But what about those for
whom such interventions have come too late? In this article, Michael Peake explains why it is important to be alert to lung cancer
Identify knowledge gaps
Figure 1: A chest X-ray is a cheap diagnostic tool for lung cancer
ung cancer is a term that covers a variety
of malignant tumours within the lungs
and the surrounding pleural membrane,
although it excludes the asbestos-related
pleural tumour, malignant mesothelioma. It is
one of the most common forms of cancer
and the commonest cause of cancer-related
death, with an estimated 1.18 million people
dying worldwide from the disease in 2002.1
In the same year, there were 33,600 deaths
from lung cancer in the UK, making up 22
per cent of all cancer deaths.2 This compares
with 12,900 deaths from breast cancer, 16,200
from colorectal cancer and 9,900 from
prostate cancer2 — lung cancer now exceeds
breast cancer as the most common cause of
death from cancer in women in many parts of
the world, including the UK. These facts are
not well publicised and a long-standing lack
of media interest in lung cancer has resulted
in a low level of public awareness.
The incidence of lung cancer and death
from it in males increased steadily between
the 1950s and the end of the ’80s but since
then it has steadily fallen — the decline has
not yet plateaued. In women, the incidence
has always been below that in men, but this
has steadily increased since the 1970s. The
male to female ratio has shifted from almost
6:1 in the early 1970s to around 2:1 in the
early 2000s. These trends parallel the trends
in the prevalence of smoking in both sexes
over the period, though with a 20–25 year lag
time.
The mean age at diagnosis is around 70
years but this means, of course, that half of the
cases occur in individuals younger than 70
years old and patients with lung cancer in
Before reading on, think about how this article may
help you to do your job better. The Royal
Pharmaceutical Society’s areas of competence for
pharmacists are listed in “Plan and record”,
(available at: www.rpsgb.org/education). This
article relates to “common disease states” and
“health education and promotion” (see appendix 4
of “Plan and record”).
L
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1. What symptoms or signs could indicate
possible lung cancer?
2. Can you list two types of lung cancer?
3. What are the treatment options for lung cancer?
their 40s and 50s are common in clinical
practice.
Across the UK there is wide variation in
the incidence of lung cancer and there is a
strong correlation between socio-economic
status and its frequency in the population, the
highest incidences being in the lowest socioeconomic groups.The fact that lung cancer is
most common in older, male, working class
smokers probably explains why it is of less
interest to the media than breast cancer.
Risk factors and prevention
Michael Peake MBChB,
FRCP, is consultant and
senior lecturer in
respiratory medicine at
Glenfield Hospital,
Leicester, and the Cancer
Services Collaborative
national clinical lead for
lung cancer
Around 90 per cent of lung cancers in men
and 80–85 per cent in women are believed to
be caused by cigarette smoking. This means,
however, that every year in the UK between
4,000 and 5,000 people who have never
smoked die of lung cancer — this is more than
the number of people who die of lymphoma,
leukaemia, ovarian cancer, cervical cancer, etc
— and it is believed that at least 20 per cent of
these deaths are related to passive smoking.
There is a strong correlation between the
number of cigarettes smoked and duration of
smoking and the risk of developing lung cancer. Between one in six and one in seven lifelong smokers will die of the disease.
Continuing professional development
An overview of lung cancer
28 October 2006 The Pharmaceutical Journal (Vol 277) 521
Other risk factors for lung cancer include
exposure to asbestos or radon. People who
may have been exposed to asbestos include
those who have worked in ship building, insulation, boiler making or repair, carpentry or
demolition industries.
Patients with chronic obstructive pulmonary disease (COPD) are also at significantly high risk of developing lung cancer and
this excess risk is independent of their smoking history. In addition, patients with a previous history of cancer (especially head or neck)
are considered a high-risk group.
There is a small increased likelihood of
developing lung cancer if there is a family
history, but the excess risk is much smaller
than with breast cancer.
Panel 1: Common
symptoms of lung
cancer
■
■
■
■
Haemoptysis
Cough
Breathlessness
Chest or shoulder pain, or
both (this is usually a
continuous dull ache but
at times can be sharp
and worse on inspiration)
■ Weight loss
■ Hoarseness
■ Fatigue
Symptoms and signs
In its early stages, lung cancer usually causes
little in the way of symptoms. Because it is a
deep internal tumour, it can grow to a considerable size in many patients before medical
advice is sought. Research is ongoing into various methods of screening and early detection
but routine screening is, as yet, of unproven
value and is unlikely to become available in
the foreseeable future, at least in the UK. It is
essential, therefore, that all health care professionals and the general public are aware of the
early symptoms of the disease and the fact that
curative treatment is more likely to be possible
the earlier a specialist is seen.
Many of the symptoms of lung cancer are
non-specific and their onset is often gradual.
The situation is made more complex because
many smokers attribute these early symptoms
to the effects of smoking itself (eg, a “smoker’s
cough” and breathlessness).The most common
symptoms of lung cancer are shown in Panel
1. One of the slogans used by the UK Lung
Cancer Coalition is “There is no such thing as
a smoker’s cough”. In other words, one should
always look for the cause of a cough and
breathlessness, and not just put it down to the
“side effects” of smoking. Pain, weight loss,
fatigue and severe breathlessness are later stage
symptoms. Anybody with symptoms for
longer than three weeks should be referred.
In addition, it is not only new symptoms
that are important. Many smokers have some
degree of COPD, one element of which is
chronic bronchitis, and this can cause chronic
cough. However, patients with lung cancer
often say that the cough has changed recently
— for example, it becomes more productive
or frequent (eg, it might wake them at night or
interfere with talking), it is associated with a
different “noise” or, of course, their sputum
becomes streaked with blood. So changes in
chronic symptoms can also serve as a warning.
Pharmacists see many people wanting to
buy antitussives. It is vital that those with a
persistent cough see their GPs.
Diagnosis and staging
Some patients with lung cancer are detected
incidentally because a chest X-ray or a computerised tomography scan is carried out for
another purpose and this group often have
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The Pharmaceutical Journal (Vol 277) 28 October 2006
Clubbing of the
fingers can be a sign
of lung cancer
Panel 2: Common
tests in diagnosis
and staging
■ Chest X-ray
■ Computerised
tomography (CT)
scanning of thorax and
upper abdomen
■ Bronchoscopy
■ CT guided lung biopsy
■ PET-CT (positron
emission tomography)
scanning
■ Mediastinal node
sampling
■ Pleural aspiration and
biopsy
■ Assessment of lung
function (eg, spirometry)
earlier stage disease. However, as already mentioned, lung cancer more often presents late
to specialist care and, although this is partly
explained by the pattern of symptoms, there
are well documented delays caused by the
lack of awareness of health care professionals.3
A chest X-ray is a cheap, simple and easily
available test that shows abnormalities in most
patients with lung cancer who have symptoms
(see Figure 1, p521), although a normal film
does not rule out the diagnosis. GPs therefore
need to have a low threshold for requesting a
chest X-ray in patients in high risk groups
with suspicious symptoms. Pharmacists could
help promote this practice by suggesting this
to patients, thus empowering them.
Most patients suspected of having lung
cancer in primary care are referred to a local
rapid access lung cancer clinic, a network of
facilities that have developed in response to
the National Cancer Plan and the
Government’s two-week wait policy.4 The
main purposes of investigations from this
point onwards are:
■ To establish a tissue diagnosis of lung cancer and its cellular subtype
■ To exclude other diagnoses
■ To establish the stage of the disease
■ To establish the fitness of the patient for
the optimum therapy
Investigations commonly used in this
process are listed in Panel 2.
Lung cancer is a deep, internal tumour
which is not always easy to access in order to
obtain tissue for pathological examination. It
also commonly occurs in older people who
have a high incidence of co-morbidities, such
as COPD and ischaemic heart disease, making invasive investigation problematic.
Because of these various complexities, the
diagnostic pathway must be well planned and
monitored to ensure patients are treated as
quickly as possible, as well as to meet the
Government waiting time targets.5
Establishing the stage of the disease is crucial to deciding the optimum treatment and is
a major element in determining the prognosis (see below). Non-small cell lung cancer
(see below) is staged using the international
TNM (tumour, nodes, metastases) classification (see Panel 3). Only patients with stages I
and II are usually suitable for surgical treatment. In most centres in the UK these patients comprise less that 20 per cent of those
referred — most patients already have incurable disease by the time they reach specialist
care. Spread (metastasis) of lung cancer is usually first to the mediastinal lymph nodes then,
in approximate order of frequency, to the
liver, adrenal glands, bones and brain.
Types of lung cancer
Lung cancers almost always develop in the
mucosa of the bronchi and smaller airways
that are exposed to inhaled carcinogens, particularly cigarette smoke. A number of different types of cell line the airways and when
they undergo malignant transformation they
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The lungs consist of six lobes,
three on each side. Lymphatic
drainage from these is into
lymph nodes in the hilar regions
(ie, where the main airways and
blood vessels come together
near the middle of the thorax).
These then drain into nodes in
the mediastinum, the core of the
thorax around the trachea and
major vessels.
Hilar lymph
nodes
and to palliate symptoms, which can worsen as
the disease progresses.
Aorta
Right main
bronchus
Left main
bronchus
Mediastinal
lymph nodes
result in different types of cancer. The most
common types of lung cancer are:
■
■
■
■
■
Small cell lung carcinoma is becoming less
common and is characterised by relatively
rapid growth and early spread to other
organs. It is strongly associated with smoking.
The other types of lung cancer (squamous
cell carcinoma, adenocarcinoma and large cell
carcinoma) are often grouped together for
practical purposes and labelled as “non-small
cell lung cancer” (NSCLC), the most common subtypes being squamous cell carcinoma
and adenocarcinoma. Squamous cell carcinoma is common in smokers whereas the
association between smoking and adenocarcinoma is less strong.
Prognosis
Cancer therapy
An article on pp518–25
describes targeted therapy
for cancer.
Panel 3: Summary of staging of NSCLC
Stages I and II (early stages) Primary tumour confined to one lung lobe with lymph node
involvement limited to hilar nodes
Stage IIIA Locally more advanced with involvement of mediastinal lymph nodes
Stage IIIB Locally more advanced, sometimes with pleural effusion (accumulation of
fluid between the pleura) and involvement of contralateral mediastinal lymph nodes
Stage IV Metastases to other organs (including other parts of the lungs)
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There are several major types of treatment6 for
lung cancer: surgery, radiotherapy, chemotherapy, biological agents and palliative care.
Combination treatment with two or more of
these can be used. All these therapies (including chemotherapy) have been demonstrated
either to improve quality of life or not to
make it worse in the context of modest improvements in survival. In patients for whom
there is no prospect of cure there is, therefore,
a trade-off between these benefits and side
effects and the inconvenience of treatment.
Surgery Suitability for surgery depends both
on the patient having “technically resectable”,
non-metastatic NSCLC (usually stages I or II)
and being fit for major surgery.Technically resectable means that the surgeon is able to
remove all the visible tumour without major
damage to vital organs. However, many
patients are old and have smoking-related comorbidities so are not fit for surgery (either
they are unfit for a general anaesthetic or they
would not be able to survive on the smaller
volume of lung that would remain). Only 8
per cent of patients with lung cancer are
treated with surgical resection in UK, a lower
figure than in many other western countries.
There is also wide variation in resection rates
within the UK itself, with up to 20 per cent of
patients having surgery in some centres compared with below 5 per cent in others. It is not
clear to what extent this variation can be
explained by the case-mix of patients, but it is
likely that differences in access to specialist
thoracic surgery also has a part to play.
In terms of small cell lung cancer, surgery
is controversial. Most surgeons do not perform
resections because a high proportion of
patients have metastatic disease undetected at
the time of surgery. However, small small cell
lung cancers where a PET scan shows no
metastases are resected in some centres and the
results are good.
Squamous cell carcinoma (~50 per cent)
Adenocarcinoma (~30 per cent)
Large cell carcinoma (<5 per cent)
Small cell carcinoma (~15 per cent)
Rare tumours (<5 per cent)
The overall prognosis of lung cancer is poor.
Nearly 50 per cent of patients die within six
months of diagnosis and this is largely the
result of late presentation, with over twothirds of patients having metastatic disease at
diagnosis. In those with early stage disease
NSCLC (stages I or II), most of whom are
treated by surgery, between 50 and 70 per
cent survive beyond five years. It is, therefore,
essential that patients are identified and
referred for specialist care as quickly as possible. However, even in patients who are not
suitable for potentially curative treatment
there is much that can be done to increase
medium-term survival (one to three years)
Treatment
Radiotherapy Some patients who are unfit
for surgery may be fit for radical (high-dose)
radiotherapy. Radiotherapy can also be used as
a palliative treatment for patients without any
realistic prospect of long-term survival (ie, beyond five years). Such palliative radiotherapy is
particularly useful in patients with bone pain,
large airway narrowing, symptoms from cerebral metastases and persistent haemoptysis.
Continuing professional development
Lung anatomy
Chemotherapy Chemotherapy is the first
line treatment for most patients with small cell
lung cancer, most of whom will have a prompt
and clinically useful response, both in terms of
shrinkage in the size of the tumour and
improvement in symptoms. This response is
often relatively short-lived, but there are
significant improvements in survival, with
treatment adding months of life for many
patients and leading to survival well beyond
two years in a minority.
28 October 2006 The Pharmaceutical Journal (Vol 277) 523
Chemotherapy is also used in NSCLC. It is
of modest but proven benefit in terms of
increasing long-term survival in patients who
undergo surgery — this is called “adjuvant
chemotherapy.” In advanced disease stages
(IIIB and IV), it provides useful palliation of
symptoms in most patients and a modest
improvement in survival.The median survival
(ie, the time in months when only 50 per cent
of patients remain alive) is increased by 10–12
weeks, but the proportion who survive to one
year is doubled.
In NSCLC the most common first-line
chemotherapy is a doublet (sometimes a
triplet) containing a platin (cisplatin or carboplatin) and vinorelbine, gemcitabine or paclitaxel. In locally more advanced NSCLC (stage
IIIA and some IIIB) there is good evidence
that a combination of chemotherapy and
radiotherapy can significantly improve survival
with a few patients surviving beyond five years.
Biological agents Biological agents are a
new and exciting heterogenous group of
drugs. In the past few years there have been
huge advances in the understanding of how
tumours develop, grow and spread and many
biochemical pathways that drive the various
components of these processes have been
identified. Clearly, if key elements of a tumour
growth pathway can be identified, there is the
potential to block or inhibit growth using
drug therapy.
The two most promising receptors that
have been identified to date are epidermal
growth factor receptors (EGFR) and vascular
endothelial growth factor (VEGF) receptors.A
large number of agents that block these receptors when they bind to them, either by biochemical means or as monoclonal antibodies,
are being studied.The first to receive a licence
in the UK was erlotinib (Tarceva), an EGFR
antagonist. This is an oral preparation that has
been demonstrated to lead to a significant improvement in survival and symptom palliation
in patients with advanced NSCLC who have
relapsed after first and second line chemotherapy. A small proportion of patients indeed experience a dramatic response. The side effects
are largely limited to skin rash and diarrhoea
— much less troublesome than those associated with conventional chemotherapy.
Palliative care Since most patients with
lung cancer are unlikely to be cured of their
disease and distressing symptoms are common,
high quality specialist palliative care is a vital
part of any lung cancer service.Apart from the
more well-known elements of palliative care
such as relief of pain and breathlessness, there
are a variety of specialist interventions that can
have a major impact on quality of life. These
include stenting of larger airways and the
superior vena cava and laser treatment of large
airway obstruction. Many such techniques are
only available in specialist centres.
Follow-up
After treatment, patients are followed up on a
regular basis by their oncologist or surgeon
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The Pharmaceutical Journal (Vol 277) 28 October 2006
Action: practice
points
Reading is only one way to
undertake CPD and the
Society will expect to see
various approaches in a
pharmacist’s CPD portfolio.
1. Think about your line of
questioning when selling
products for cough and,
where appropriate, make
sure people know they can
ask their GP for a chest
X-ray.
2. November is lung cancer
awareness month.
Increase awareness in
your pharmacy. Leaflets
and posters are available
at www.roycastle.org/
patient/lcam.htm
3. Set up a smoking
cessation service.
Evaluate
For your work to be presented
as CPD, you need to evaluate
your reading and any other
activities. Answer the
following questions:
What have you learnt?
How has it added value to
your practice? (Have you
applied this learning or had
any feedback?) What will you
do now and how will this be
achieved?
Resource
■ National Institute for Health and
Clinical Excellence. Referral for
suspected cancer. Available at
www.nice.org.uk (accessed 18
October 2006).
References
1. Parkin DM, Bray F, Ferlay J, Pisani P.
Global cancer statistics, 2002.
Cancer Journal for Clinicians
2005;55:74–108.
2. Toms JR (editor). CancerStats
Monograph, London: Cancer Research
UK; 2004.
3. Birring SS, Peake MD. Symptoms and
the early diagnosis of lung cancer.
Thorax 2005 60:268–9.
4. Department of Health. The NHS
national cancer plan. London:
Department of Health; 2000.
5. Department of Health. Waiting times
for cancer – progress, lessons learnt
and next steps. London: Department
of Health; 2006.
6. National Institute for Health and
Clinical Excellence. Diagnosis and
treatment of lung cancer. Available at
www.nice.org.uk (accessed 18
October 2006).
and consideration is given to second-line
treatments, including chemotherapy, palliative
radiotherapy or erlotinib, if there is evidence
of recurrence.
The chances of response to second (and
subsequent) lines of treatment are less than
are associated with first-line treatment and
toxicity can be worse, so careful assessment of
each patient is essential to decide the potential benefits of a treatment. Patients usually
remain under follow up, though at increasing
intervals, until either they die or have survived five years.
Conclusion
Early detection of lung cancer is one of the
major ways in which overall outcomes can be
improved. Methods of screening high-risk
patient groups are being studied, including
the use of low-dose CT screening and sputum cytometry (an advanced form of sputum
cytology using automated molecular biological techniques). Increased awareness of early
symptoms of the disease will be an important
element of any such strategy.
The biology of lung cancer is being
unravelled and we are now in sight of being
able to target treatment more precisely.This is
already beginning to happen with the EGRF
antagonist erlotinib mentioned above.
Moreover, better standards and organisation
of care resulting from the National Cancer
Plan are beginning to make a major difference to the quality of care and outcomes for
lung cancer patients. However, there is still
much more that can be done.
Reducing the numbers of people who
start smoking would clearly have a major
impact on the incidence of lung cancer, but
stopping smoking also significantly reduces
the risk of developing lung cancer so the
obvious way in which pharmacists can contribute in the area of lung cancer is to support
smokers to give up. If we could stop a significant proportion of 50-year-olds smoking, it
would result in a major reduction in the mortality from the disease.
However, pharmacists working in the
community also advise patients with respiratory symptoms. They should advise those
with persistent cough or dyspnoea to seek
urgent medical advice and to consider asking
their GP for a chest X-ray. I suspect that if
pharmacists were more alert to the symptoms
of lung cancer and the characteristics of the
at-risk groups and took a proactive approach,
many more patients could be detected earlier
in the course of their disease and would,
therefore, have a greater chance of curative
treatment. Next time you advise a customer
with a cough, think about the following:
■ Is he or she over 50 years old?
■ Is he or she a smoker or ex-smoker?
■ Does he or she have COPD or
symptoms?
■ Could he or she have been exposed to
asbestos?
■ Could he or she have a previous history
of cancer?
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Correction
The left lung has two lobes and not three as stated
in this Continuing Professional Development
article. The right lung has three lobes. This can be
important when viewing chest X-rays.